Field
The present disclosure relates to novel phytosphingosine derivatives and compositions comprising the same, for preventing and treating inflammatory skin diseases and autoimmune diseases, and more particularly, to phytosphingosine derivatives of Chemical Formulas IA and IB, and compositions comprising the same for preventing and treating inflammatory skin diseases, autoimmune diseases, and hyperkeratotic disorders.
Discussion of the Background
Phytosphingosine is a lipid having a skeletal structure of spingosine, which is abundant in fungi, plants, and the skin of animals including humans. In particular, phytosphingosine serves as a precursor of ceramide, which is an integral part of the lipid bilayer of the stratum corneum of the skin, to prevent the moisture loss from the skin, thereby moisturizing the skin and preventing easy absorption of foreign harmful materials into the dermal layer of the skin. In addition, phytosphingosine is absorbed in the body to promote the synthesis of ceramides, and has antimicrobial activity against several microorganism including Propionibacterium acnes and Staphylococcus aureus, and thus, is included in products for the treatment of acne and the like.
Phytosphingosine and phytosphingosine derivatives such as N-acetyl phytosphingosine (NAPS) and tetra-acetyl phytosphingosine (TAPS) regulate the expression of cyclooxygenase-2 (COX-2) in skin keratinocytes, induce apoptosis through activation of caspase-8 and mitochondria, suppress skin keratinocyte hyperproliferation against external stimuli, and regulate skin inflammation responses. However, since they cause damage to the liver and the kidneys, cause gastrointestinal disorders and accompanying dizziness and vomiting, and have severe cytotoxicity, their disadvantages due to cytotoxicity outweigh their advantages as a therapeutic agent, and as a result, they are difficult to use as an agent for treating skin diseases or other diseases.
Maleic acid is the geometric isomer (having the same molecular formula) of fumaric acid, and is used as an acidulant for giving a tart taste in juice, cider, canned fruits, and the like. Maleic anhydride generated through heating is widely used in the preparation of unsaturated polyester resins, copolymers with styrene, and various synthetic chemicals by reacting with various materials using catalysts.
The present inventors have synthesized phytosphingosine derivatives (mYG-II-6 and fYG-II-6) having an anti-inflammatory effect while overcoming disadvantages of phytosphingosine by using phytosphingosine (PS) and maleic anhydride (MA) or fumaric acid (FA), and as a result, provided materials and a pharmaceutical composition exhibiting excellent effects in the treatment and prevention of inflammatory skin diseases, autoimmune diseases, and hyperkeratotic disorders.